Optically active carboxylic acids represented by the formula ##STR2## herein R.sub.1 and R.sub.2 are each independently selected from alkyl, cycloalkyl, aralkyl or aryl, and n is 1 or 2, are useful, for example, as intermediates for the synthesis of various physiologically active materials. For example, a compound of the formula ##STR3## is a key intermediate in the synthesis of: 1-[(2S)-3-mercapto-2-methylpropionyl]-L-proline (captopril), having the formula [1(R*),2.alpha.,4.alpha.]-1-[3-(benzoylthio)-2-methyl-1-oxopropyl]-4-(phen ylthio)-L-proline (zofenopril), having the formula ##STR4## endopeptidase inhibitors having the formula ##STR5## The beneficial activities of captopril, zofenopril and endopeptidase inhibitors of the above formula, depends on the configuration of the mercaptoalkanoyl moiety and the compound of the S configuration is about 100 times more potent than the corresponding R-enantiomer.
Prior art processes for making captopril have utilized chemical and enzymatic resolution procedures. For example, carboxylic acids of formula I are prepared as racemic mixtures which can be separated into the R and S-enantiomeric forms using chemical resolving agents. The so-provided S intermediates can then be used to prepare the desired product The chemical resolution techniques have the distinct disadvantage, however, that large amounts of very expensive resolving agents are required to make the desired enantiospecific products Additionally, the processes themselves are cumbersome and the yield is relatively low.
Alternatively, racemic compounds of the formula ##STR6## can be directly coupled to L-proline and derivatives thereof having the formula ##STR7## wherein R.sub.3 is ##STR8## or --OH, and including salts and protected forms thereof, to produce diastereomers of the general formula ##STR9## The SS-diastereomer of compound V can be isolated and thereafter reacted using known methodology to provide the desired resolved products. However, a drawback to this process is that an equal amount of the RS-diastereomer of compound V is formed which must be discarded. This is highly undesirable in view of the cost of the L-proline.
U.S. Pat. No. 4,629,701 provides the desired resolved form of the carboxylic acids of formula I by subjecting an ester of the formula ##STR10## to an enzyme capable of asymmetrically hydrolyzing such an ester. It was found that while the ##STR11## moiety is hydrolyzed to the acid form, the racemic ester is also resolved into the S or R configuration in improved yields and at lower costs than possible with chemical resolution techniques. However, there is still a considerable expense in making these ester starting materials and higher optical purity is still desired for more active products. Therefore, a process which is less expensive with improved yields and which provides enhanced optical purity would be a useful addition to the art.